Lipid A of bacterial lipopolysaccharide (Lipid A)

Lipid A is the hydrophobic glycolipid anchor of bacterial lipopolysaccharide (LPS; endotoxin), found in the outer membrane of Gram-negative bacteria[1][2][4][6]. It consists of a disaccharide backbone of glucosamine units, typically phosphorylated, with multiple (often six) fatty acyl chains attached, and is highly conserved among enterobacteria but can show structural diversity across genera[1][5]. Lipid A provides essential structural integrity to the bacterial outer membrane and is the primary determinant of the potent pro-inflammatory effects and toxicity of LPS in mammals[1][2][4]. Detected as a pathogen-associated molecular pattern (PAMP) by Toll-like receptor 4 (TLR4)/MD-2/CD14 complex on innate immune cells, lipid A triggers strong host immune responses that are protective against infection but can lead to life-threatening sepsis and septic shock when dysregulated[1][2][4][7]. Drug development efforts targeting lipid A/TLR4 pathways have focused on antagonists (such as eritoran) to mitigate excessive inflammation in severe bacterial infections[1]. Lipid A is also a key target for cationic antibiotic peptides such as polymyxin B and colistin, which directly bind and neutralize the molecule[6].

Other names

Lipid Aendotoxin lipid ALPS lipid Alipopolysaccharide lipid A

Inhibition of TLR4 signaling (e.g., eritoran acts as a TLR4 antagonist by competing with lipid A for receptor binding); Neutralization of endotoxin activity (e.g., polymyxin B directly binds and inactivates lipid A)